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Targeting tumor extracellular matrix activates the tumor-draining lymph nodes

Citation:

Najibi AJ, Shih T-Y, Zhang DKY, Lou J, Sobral MC, Wang H, Dellacherie MO, Adu-Berchie K, Mooney DJ. Targeting tumor extracellular matrix activates the tumor-draining lymph nodes. Cancer Immunol Immunother. 2022;71 (12) :2957-2968.

Date Published:

2022 Dec

Abstract:

Disruption of the tumor extracellular matrix (ECM) may alter immune cell infiltration into the tumor and antitumor T cell priming in the tumor-draining lymph nodes (tdLNs). Here, we explore how intratumoral enzyme treatment (ET) of B16 melanoma tumors with ECM-depleting enzyme hyaluronidase alters adaptive and innate immune populations, including T cells, DCs, and macrophages, in the tumors and tdLNs. ET increased CD103+ DC abundance in the tdLNs, as well as antigen presentation of a model tumor antigen ovalbumin (OVA), eliciting local OVA-specific CD8+ T cell responses. Delivered in combination with a distant cryogel-based cancer vaccine, ET increased the systemic antigen-specific CD8+ T cell response. By enhancing activity within the tdLN, ET may broadly support immunotherapies in generating tumor-specific immunity.